Pimavanserin, a novel agent approved for the treatment of Parkinson’s disease psychosis, has potent actions as an antagonist/inverse agonist at serotonin 5HT2A receptors and less potent antagonist/inverse agonist actions at 5HT2C receptors.

The symptoms of emotional dysregulation associated with the syndrome known as pseudobulbar affect (PBA) can be effectively treated by the sigma, glutamate, and serotonergic agent dextromethorphan combined with quinidine. If the same brain circuits affected in PBA are also compromised in related disorders of emotional expression, dextromethorphan-quinidine and other novel sigma-glutamate-serotonin agents could prove to be novel psychopharmacologic treatments for these conditions as well.

Cariprazine is a new therapeutic agent recently approved for the treatment of both schizophrenia and manic or mixed episodes associated with bipolar disorder, and is under investigation for the treatment of both bipolar depression and major depressive disorder.

Brexpiprazole is a new therapeutic agent that was recently approved for the treatment of schizophrenia and for the adjunctive treatment of major depressive disorder. Brexpiprazole has features that both overlap and contrast with a related molecule, aripiprazole, and these features are discussed here.

There are several new and emerging medication interventions for both the acute and maintenance treatment phases of schizophrenia. Recently approved are 2 new dopamine receptor partial agonists, brexpiprazole and cariprazine, as well as 2 new long-acting injectable antipsychotic formulations, aripiprazole lauroxil and 3-month paliperidone palmitate. Although differences in efficacy compared to other available choices are not expected, the new oral options offer different tolerability profiles that may be attractive for individual patients who have had difficulties with older medications. The new long-acting injectable options provide additional flexibility in terms of increasing the time interval between injections. In Phase III of clinical development is a novel antipsychotic, lumateperone (ITI-007), that appears to have little in the way of significant adverse effects. Deutetrabenazine and valbenazine are agents in Phase III for the treatment of tardive dyskinesia, a condition that can be found among persons receiving chronic antipsychotic therapy. On the horizon are additional injectable formulations of familiar antipsychotics, aripiprazole and risperidone, that may be more convenient than what is presently available.

Parkinson’s disease psychosis (PDP) is theoretically a serotonin-dopamine imbalance syndrome due to disruption of the normal balance between the serotonergic and dopaminergic neurotransmitter systems in key brain circuits.

Suovrexant is a novel hypnotic and is the only agent clinically available that works by blocking orexin-ergic mechanisms.

The broad use of atypical antipsychotics was expected to dramatically reduce the prevalence and incidence of tardive dyskinesia (TD), but data show that TD remains an important challenge due the persistent nature of its symptoms and resistance to numerous treatment modalities, including antipsychotic discontinuation. Recent insights on genetic risk factors and new concepts surrounding pathophysiology have spurred interest in the possibility of targeted treatment for TD. As will be reviewed in this article, the number of evidence-based strategies for TD treatment is small: only clonazepam, amantadine, ginkgo biloba extract, and the vesicular monoamine transporter 2 (VMAT2) inhibitor tetrabenazine have compelling data. Using new insights into the metabolism of tetrabenazine and the properties of its active metabolites, 2 modifications of tetrabenazine have been synthesized to improve the kinetic profile, and are currently involved in double-blind placebo controlled studies aimed at U.S. Food and Drug Administration (FDA) regulatory approval. The possible availability of these new agents, deuterated tetrabenazine and valbenazine, significantly widens the range of treatment choices for patients with TD. For clinicians with patients at risk for TD due to dopamine antagonist exposure, experience has shown that the problem of TD will be an ongoing issue in modern psychiatry, and that an appreciation of new developments in the pathophysiology of, risk factors for, and treatment of TD is crucial to managing this condition.

Seclusion may be harmful and traumatic to patients, detrimental to therapeutic relationships, and can result in physical injury to staff. Further, strategies to reduce seclusion have been identified as a potential method of improving cost-effectiveness of psychiatric services. However, developing alternative strategies to seclusion can be difficult. Interventions to reduce seclusion do not lend themselves to evaluation using randomized controlled trials (RCTs), though comprehensive literature reviews have demonstrated considerable non-RCT evidence for interventions to reduce seclusion in psychiatric facilities. In the UK, a recent 5-year evaluation of seclusion practice in a high secure UK hospital revealed reduced rates of seclusion without an increase in adverse incidents. To assess the effect of a novel intervention strategy for reduction of long-term segregation on a high secure, high dependency forensic psychiatry ward in the UK, we introduced a pilot program involving stratified levels of seclusion (“long-term segregation”), multidisciplinary feedback and information sharing, and a bespoke occupational therapy program. Reduced seclusion was demonstrated and staff feedback was mainly positive, indicating increased dynamism and empowerment on the ward. A more structured, stratified approach to seclusion, incorporating multidisciplinary team-working, senior administrative involvement, dynamic risk assessment, and bespoke occupational therapy may lead to a more effective model of reducing seclusion in high secure hospitals and other psychiatric settings. While lacking an evidence base at the level of RCTs, innovative, pragmatic strategies are likely to have an impact at a clinical level and should guide future practice and research.

The two main diagnostic systems, the International Classification of Diseases (ICD) and the Diagnostic and Statistical Manual of Mental Disorders (DSM), have undergone a number of revisions since their first editions: whereas the fifth edition of the DSM has been published in 2013, the eleventh revision of the ICD is expected by 2018. Although the process of harmonization between the 2 systems is still a debated topic, the forthcoming revision of the ICD is seemingly converging toward the DSM approach in regard to the reclassification of a number of disorders. Nevertheless, the 2 systems still exhibit considerable differences, partly due to their different purposes, development and revision processes, and target audiences. Furthermore, while alternative and innovative classification approaches are emerging with the aim of integrating the latest findings from neuroscience and genomics, both the DSM and ICD still fail to incorporate core concepts such as the clinical staging of psychiatric disorders and “neuroprogression,” as well as an adequate consideration of endophenotypes.

Mixed features specifier (MFS) is a new nosological entity defined and operationalized in the Diagnostic and Statistical Manual of Mental Disorders (DSM), 5th Edition. The impetus to introduce the MFS and supplant mixed states was protean, including the lack of ecological validity, high rates of misdiagnosis, and guideline discordant treatment for mixed states. Mixed features specifier identifies a phenotype in psychiatry with greater illness burden, as evidenced by earlier age at onset, higher episode frequency and chronicity, psychiatric and medical comorbidity, suicidality, and suboptimal response to conventional antidepressants. Mixed features in psychiatry have historical, conceptual, and nosological relevance; MFS according to DSM-5, is inherently neo-Kraepelinian insofar as individuals with either Major Depressive Disorder (MDD) or Bipolar Disorder (BD) may be affected by MFS. Clinicians are encouraged to screen all patients presenting with a major depressive episode (or hypomanic episode) for MFS. Although “overlapping symptoms” were excluded from the diagnostic criteria (eg, agitation, anxiety, irritability, insomnia), clinicians are encouraged to probe for these nonspecific symptoms as a possible proxy of co-existing MFS. In addition to conventional antidepressants, second generation antipsychotics and/or conventional mood stabilizers (eg, lithium) may be considered as first-line therapies for individuals with a depressive episode as part of MDD or BD with mixed features.

One of the main changes in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) was the separation of Stress Related Disorders from the Anxiety chapter. This separation paves the way to examine the unique characteristics of posttraumatic stress disorder (PTSD) (ie, identifiable onset, memory processes, etc) and related neural mechanisms. The time that elapses between the traumatic event and the manifestation of the disorder may also be addressed as the “golden hours,” or the window of opportunity in which critical processes take place and relevant interventions may be administrated.